*Article* **Evolution of Gut Microbiome and Metabolome in Suspected Necrotizing Enterocolitis: A Case-Control Study**

**Camille Brehin 1,2, Damien Dubois 2,3, Odile Dicky 4, Sophie Breinig 5, Eric Oswald 2,3 and Matteo Serino 2,\***


Received: 2 June 2020; Accepted: 15 July 2020; Published: 17 July 2020

**Abstract:** Background: Necrotizing enterocolitis (NEC) is a devastating condition in preterm infants due to multiple factors, including gu<sup>t</sup> microbiota dysbiosis. NEC development is poorly understood, due to the focus on severe NEC (NEC-2/3). Methods: We studied the gu<sup>t</sup> microbiota, microbiome and metabolome of children with suspected NEC (NEC-1). Results: NEC-1 gu<sup>t</sup> microbiota had a higher abundance of the Streptococcus (second 10-days of life) and Staphylococcus (third 10-days of life) species. NEC-1 children showed a microbiome evolution in the third 10-days of life being the most divergent, and were associated with a di fferent metabolomic signature than in healthy children. The NEC-1 microbiome had increased glycosaminoglycan degradation and lysosome activity by the first 10-days of life, and was more sensitive to childbirth, low birth weight and gestational age, than healthy microbiome. NEC-1 fecal metabolome was more divergent by the second month of life. Conclusions: NEC-1 gu<sup>t</sup> microbiota and microbiome modifications appear more distinguishable by the third 10-days of life, compared to healthy children. These data identify a precise window of time (i.e., the third 10-days of life) and provide microbial targets to fight/blunt NEC-1 progression.

**Keywords:** necrotizing enterocolitis; intestinal microbiology; microbiome; infant gut; metabolomics
